"Effectiveness of Combined Chemotherapy and Keytruda Treatment in HER2-Negative Advanced Gastric Cancer"

The therapeutic effect of immune checkpoint inhibitors has been demonstrated in HER2-negative advanced gastric cancer.

Professor Ra Sun-young's team in the Department of Medical Oncology at Yonsei Cancer Hospital's Gastric Cancer Center conducted a study on HER2-negative advanced gastric cancer patients using a combination therapy of the immune checkpoint inhibitor 'Keytruda' with conventional chemotherapy. The results showed an overall survival of 12.9 months, an objective response rate of 51.3%, and a duration of response of 8 months, demonstrating superior efficacy compared to existing treatments and a 22% reduction in the risk of death.
[Image provided by Severance Hospital]

Professor Sunyoung Ra's team from the Department of Oncology at Yonsei Cancer Hospital's Gastric Cancer Center conducted a study on HER2-negative advanced gastric cancer patients. They administered a combination therapy of the immune checkpoint inhibitor 'Keytruda' with conventional chemotherapy. The results showed an overall survival of 12.9 months, an objective response rate of 51.3%, and a duration of response of 8 months, indicating superior efficacy compared to existing treatments and a 22% reduction in the risk of death.

The research team explained that the incidence of gastric cancer is particularly high in Asia. According to the 2020 National Cancer Registry statistics, gastric cancer ranked fourth in incidence (10.8%) and, along with lung, liver, and colorectal cancers, has a high mortality rate. In Western countries, which lead new drug development, the incidence of gastric cancer is lower than in Asia, resulting in delayed development of targeted therapies for gastric cancer. Advanced gastric cancer is classified as HER2-positive or HER2-negative based on HER2 expression. Approximately 85% of patients are HER2-negative, most of whom have stage IV gastric cancer and receive conventional toxic chemotherapy as standard first-line treatment. However, this therapy is known to have a poor prognosis.

The research team conducted the global phase 3 clinical trial 'KEYNOTE-859' to compare the efficacy of first-line combination therapy of Keytruda and chemotherapy versus chemotherapy alone in HER2-negative gastric cancer patients. A total of 1,579 patients were randomly assigned, with each patient receiving either Keytruda (200 mg every 3 weeks for up to approximately 2 years) in combination with chemotherapy or chemotherapy alone.

The study results showed that the combination therapy demonstrated clinically significant improvements not only in the primary endpoint of overall survival (OS) but also in secondary endpoints including progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety compared to monotherapy.

Evaluation variable results of Keytruda combination therapy and chemotherapy monotherapy in patient groups with PD-L1 CPS expression rates of 1 and 10 or higher.
[Image provided by Severance Hospital]

After an average follow-up of 31 months, combination therapy reduced the risk of death by 22% compared to monotherapy regardless of the expression of PD-L1, a protein that suppresses immune cell activation in gastric cancer cells. The median OS for the primary endpoint was 12.9 months for the combination therapy, showing improvement over 11.5 months for monotherapy. For the secondary endpoint, progression-free survival was 6.9 months with combination therapy versus 5.6 months with monotherapy, and the objective response rate was higher at 51.3% compared to 42%. The duration of response to the drug was also longer with combination therapy at 8 months versus 5.7 months for monotherapy.

Notably, the Keytruda combination therapy showed greater improvement in patients with higher PD-L1 expression. The research team confirmed that in patient groups with a PD-L1 combined positive score (CPS) of 1 or higher and 10 or higher, the Keytruda combination therapy demonstrated superior treatment effects across all evaluation parameters compared to monotherapy.

Professor Ra stated, "Following the previously published results on Opdivo, this global phase 3 study has proven the long-term survival benefits of immune checkpoint inhibitors in HER2-negative advanced gastric cancer. We expect to offer a safe and improved treatment strategy to patients who have had limited treatment options until now."

Meanwhile, the study results were published in the latest issue of the international journal Lancet Oncology.

Professor Ra Sun-young, Department of Oncology, Yonsei Cancer Center.
[Photo by Severance Hospital]

This content was produced with the assistance of AI translation services.